Vitamin D Metabolism, Rickets, and Osteomalacia

Jacqueline L. Berry; Michael Davies; Andrew P. Mee

doi:10.1055/s-2002-36714

Seminars in Musculoskeletal Radiology, Table of Contents

Semin Musculoskelet Radiol 2002; 06(3): 173-182
DOI: 10.1055/s-2002-36714

Vitamin D Metabolism, Rickets, and Osteomalacia

Jacqueline L. Berry, Michael Davies, Andrew P. Mee

Vitamin D Research Group, University School of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom

Abstract

ABSTRACT

Rickets in the growing child or adolescent and osteomalacia in the adult develop in a variety of clinical situations and have in common an absence or delay in the mineralization of growth cartilage and in newly formed bone collagen. Classically, deficiency of vitamin D, which is essential for the absorption of dietary calcium, has been the major cause. However, rickets is also seen as a result of hereditary defects in critical vitamin D signaling molecules. Disturbances of phosphate metabolism can also lead to signs of rickets and osteomalacia, notably X-linked hypophosphatemic rickets, and oncogenic osteomalacia. Extrarenal synthesis of 1,25-dihydroxyvitamin D, such as that associated with granulomatous disease, can also lead to disturbances in calcium metabolism, with associated skeletal and nonskeletal changes.

KEYWORD

Vitamin D - rickets - osteomalacia - X-linked hypophosphatemic rickets - oncogenic osteomalacia

Full Text

References

REFERENCES

1 Mawer E B. The sunshine vitamin-how a dose of sunshine forms vitamin D. Biol Sci Rev . 1990; 2 2-7
2 Holick M F. Photobiology of vitamin D. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 33-39
3 Stanbury S W, Mawer E B, Lumb G A. Some aspects of vitamin D metabolism in man. In: Taylor S, ed. Endocrinology London: Heinemann Medical Books 1971: 487-499
4 Horst R L, Reinhardt T A. Vitamin D metabolism. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 13-31
5 Okuda K I, Usui E, Ohyama Y. Recent progress in enzymology and molecular biology of enzymes involved in vitamin D metabolism. J Lipid Res . 1995; 36 1641-1652
6 Fraser D R, Kodiceck E. Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature . 1970; 288 764-766
7 Minghetti P P, Norman A W. 1,25(OH)₂-vitamin D3 receptors: gene regulation and genetic circuitry. Fed Am Soc Exp Biol J . 1988; 2 3043-3053
8 Haussler M R, Haussler C A, Thompson P D. Molecular nature of the vitamin D receptor and its role in regulation of gene expression. Rev End Met Dis . 2001; 2 203-215
9 Adams J S, Lemire J, Gacad M A, Hewison M. Vitamin D as cytokine and haematopoetic factor. Rev End Met Dis . 2001; 2 217-227
10 Wasserman R H. Vitamin D and the intestinal absorption of calcium and phosphorus. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 259-273
11 Barbour G L, Coburn J W, Slatopolsky E, Norman A W, Horst R L. Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D. N Eng J Med . 1981; 305 440-443
12 Hayes M E, Denton J, Freemont A J, Mawer E B. Synthesis of the active metabolite of vitamin D, 1,25(OH)₂D3, by synovial fluid macrophages in arthritic diseases. Ann Rheum Dis . 1989; 48 723-729
13 Gkonos P J, London R, Hendler E D. Hypercalcemia and elevated 1,25-dihydroxyvitamin D levels in a patient with end-stage renal disease and active tuberculosis. N Eng J Med . 1984; 311 1683-1685
14 Fu G K, Lin D, Zhang M YH. Cloning of human 25-hydroxyvitamin D-1 α-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol . 1997; 11 1961-1970
15 Smith S J, Rucka A J, Berry J L. Novel mutations in the 1α-hydroxylase (p450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages. J Bone Min Res . 1999; 14 730-739
16 Mawer E B, Davies M. Vitamin D nutrition and bone disease in adults. Rev End Met Dis . 2001; 2 153-164
17 Holick M F. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endo Diabetes . 2002; 9 87-98
18 Hebert S C, Brown E M. The extracellular calcium receptor. Curr Opin Cell Biol . 1995; 7 484-492
19 Hock J M, Fitzpatrick L A, Bilezikian J P. Actions of parathyroid hormone. In: Bilezikian JP, Raisz L, Rodan GA, eds. Principles of Bone Biology, 2nd edition London: Academic Press 2002: 463-481
20 Mawer E B, Davies M. Bone disorders associated with gastrointestinal and hepatobiliary disease. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 831-847
21 Mawer E B, Mughal Z. Rickets. Curr Opin Ortho . 1999; 10 354-360
22 Clements M R, Johnston L, Fraser D R. A new mechanism for induced vitamin D deficiency in calcium deprivation. Nature . 1987; 325 62-65
23 Davies M, Heys S E, Selby P L, Berry J L, Mawer E B. Increased catabolism of 25-hydroxyvitamin D in patients with partial gastrectomy and elevated 1,25-dihydroxyvitamin D levels. Implications for metabolic bone disease. J Clin Endocrinol Metab . 1997; 82 209-212
24 Dunnigan M G, Henderson J B. An epidemiological model of privational rickets and osteomalacia. Proc Nutr Soc . 1997; 56 939-956
25 Malloy P J, Pike J W, Feldman D. The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant rickets. Endo Rev . 1999; 20 156-188
26 Large D M, Mawer E B, Davies M. Dystrophic calcification, cataracts and enamel hypoplasia due to long standing, privational vitamin D deficiency. Metab Bone Dis Rel Res . 1984; 5 215-218
27 Adams J E. Radiology of rickets and osteomalacia. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 619-642
28 Parfitt A M. Vitamin D and the pathogenesis of rickets and osteomalacia. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 645-662
29 Scheinman S J, Guay-Woodford L M, Thakker R V, Warnock D G. Mechanisms of disease: genetic disorders of renal electrolyte transport. N Engl J Med . 1999; 340 1177-1187
30 Tieder M, Arie R, Modai D, Samuel R, Weissgarten J, Liberman U A. Elevated serum 1,25-dihydroxyvitamin D concentrations in siblings with primary Fanconi's syndrome. N Engl J Med . 1988; 319 845-849
31 The HYP Consortium. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. Nat Genet . 1995; 11 130-136
32 Rowe P S. The role of the PHEX (PEX) gene in families with X-linked hypophosphatemic rickets. Curr Opin Nephrol Hypertens . 1998; 7 367-376
33 Adams J E, Davies M. Intraspinal new bone formation and spinal cord compression in familial hypophosphataemic vitamin D resistant osteomalacia. Q J Med . 1986; 61 117-129
34 Davies M, Kane R, Valentine J. Impaired hearing in X-linked hypophosphatemic (vitamin D resistant) osteomalacia. Ann Int Med . 1984; 100 320-232
35 Tieder M, Modai D, Samuel R. Hereditary hypophosphatemic rickets with hypercalciuria. N Eng J Med . 1985; 312 611-617
36 Drezner M K. Phosphorous homeostasis and related disorders. In: Bilezikian JP, Raisz L, Rodan GA, eds. Principles of Bone Biology, 2nd edition London: Academic Press 2002: 321-338
37 Krausz Y. Nuclear endocrinology as a monitoring tool. Sem Nuc Med . 2001; 31 238-250
38 Hosking D J, Chamberlain M J, Whortland-Webb W R. Osteomalacia and carcinoma of the prostate with major redistribution of skeletal calcium. Br J Radiol . 1975; 48 451-456
39 McClure J, Smith P S. Oncogenic osteomalacia. J Clin Pathol . 1989; 40 446-453
40 Rathbun J C. Hypophosphatasia, a new developmental anomaly. Am J Dis Child . 1948; 75 822-831
41 Whyte M P. Hypophosphatasia: nature's window on alkaline phosphatase function in man. In: Bilezikian JP, Raisz L, Rodan GA, eds. Principles of Bone Biology, 2nd edition London: Academic Press 2002: 1229-1248
42 Sandler L M, Winearls C G, Fraher L J. Studies on the hypercalcemia of sarcoidosis. Q J Med . 1984; 53 165-180
43 Taylor R L, Lynch H J, Wysor W G. Seasonal influence of sunlight on the hypercalcemia of sarcoidosis. Am J Med . 1963; 35 67-89
44 Rizzato G, Montemurro L, Fraioli P. Bone mineral content in sarcoidosis. Semin Resp Med . 1992; 13 411-423
45 Davies M, Mawer E B, Hayes M E, Lumb G A. Abnormal vitamin D metabolism in Hodgkin's lymphoma. Lancet . 1985; 1 1186-1188
46 Davies M, Hayes M E, Liu Yin A J, Berry J L, Mawer E B. Abnormal synthesis of 1,25-dihydroxyvitamin D in patients with malignant lymphoma. J Clin Endocrinol Metab . 1994; 78 1202-1207
47 Seymour J F, Gagel R F, Hagemeister F B, Dimopoulos M A, Cabanillas F. Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin's lymphoma. Ann Intern Med . 1994; 121 633-640